Fibrinogen Philadelphia: We have continued the study of the physicochemical properties and coagulation defect of Fibrinogen Philadelphia. 131 1 labelled normal fibrinogen and 125 1 tagged Fibrinogen Philadelphia were run in acrylamide electrophoresis. The abnormal fibrinogen ran 2 to 4 mm more anodally than normal fibrinogen. A similar technique was used for simultaneous DEAE chromatography of normal fibrinogen and Fibrinogen Philadelphia. The abnormal fibrinogen eluted two tubes after the normal fibrinogen, indicating increased anionic binding. The coagulation defect of Fibrinogen Philadelphia has been shown to be due to a defect in fibrin monomer aggregation. The abnormal fibrin monomers also interfere with the aggregation of fibrin monomers prepared from normal fibrinogen. This defect is more evident when the fibrin monomers are dissolved in a buffer with high ionic strength. To further characterize the molecular defect we are planning to isolate the three chains of the abnormal fibrinogen and study their physicochemical and coagulation properties when they are compared with the normal alpha-beta-gamma chains. We are studying Prothrombin and Fibrinogen Metabolism in Patients with Hypercoagulable States in association with Dr. S. Shapiro and have performed one study in a patient with severe diffuse intravascular coagulation. Both prothrombin and fibrinogen showed a short half-line and the fractional catabolic rates of these two proteins were greatly increased. The patient was treated with Heparin and both prothrombin and fibrinogen T/2 returned toward normal. We will continue the study of prothrombin and fibrinogen metabolism in different clinical conditions thought to be associated with hypercoagulable states: 1) malignancies, 2) gram negative sepsis and 3) hemolytic anemias.